Rocky Mountain spotted fever, the most severe and widespread rickettsiosis in the United States, and boutonneuse fever, a spotted fever group rickettsiosis with an extremely widespread geographic distribution in Africa, Asia, and Europe, are neglected diseases of public health importance. Toward the longterm goal of elucidation of the molecular structure and function of spotted fever group rickettsiae, this proposed research is foccussed on the identification of the antigenic proteins of Rickettsia rickettsii, R. conorii and R. montana, and on the investigation of which of these antigens are most likely to stimulate protective immunity against Rocky Mountain spotted fever and boutonneuse fever. The Western blot technique will be utilized to detect which protein antigens stimulate a humoral immune response during naturally occurring infections of humans and experimental infections of animals. A molecular study of the antigenic proteins of R. rickettsii should be facilitated by the availability of monoclonal antibodies to this rickettsia which have been developed in our laboratory. The application of Western blot methods to antigens of frequently occurring nonpathogenic spotted fever group rickettsiae should answer questions concerning the immunobiology of the competition of R. montana, R. bellii, and R. rickettsii for the same ecologic niche. The much more frequent exposure of mammals including man to R. montana, which confers crossprotection of guinea pigs against R. rickettsii, and to R. bellii, which does not confer such crossprotection, may offer clues to biologic control of the spotted fever group rickettsioses. Similarly, boutonneuse fever offers a wealthy source of strains of R. conorii of varying virulence for evaluation of antigenic proteins. The demonstration of blotted proteins by convalescent but not acute sera from humans, guinea pigs, and dogs indicates which of the proteins stimulate antibodies correlating with acquired immunity. The ultimate result of these experiments should be the collection of data needed for the rational design of vaccines to prevent spotted fever group rickettsiosis.